The role of the serotonergic neuronal system on blood pressure control of normotensive WKY rats and spontaneously hypertensive rats (SHR) was studied by injecting L-tryptophan, the metabolic precursor to brain serotonin. It was observed that the dose- and temporal effects of tryptophan on blood pressure were not related to the effects of tryptophan oon serotonin levels throughout the brain. The dextro-rotary isomer of tryptophan was no different from L-tryptophan in its ability to increase brain serotonin but D-tryptophan does not alter blood pressure in SHR or WKY. An analog of tryptophan, TR 3369, wherein the carboxyl group has been moved from the alpha to the beta carbon of the side chain, dramatically lowers blood pressure in the SHR without influencing 5-HT neurochemistry. Other peripheral metabolites of tryptophan including kynurenin and kynuramine, also lower blood pressure. Taken together, these results indicate that the cardiovascular effects of L-tryptophan are not mediated by brain serotonin and may result from direct effects of the amino acid itself or a primary metabolite on the vasculature.